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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2011  |  Volume : 22  |  Issue : 1  |  Page : 179-184
Immune response to hepatitis B vaccine in health-care workers

1 Gastroenterintestinal and Liver Disease Research Center, Iran University of Medical Sciences, Tehran, Iran
2 Baqiyatallah Research Center for Gastroenterology and Liver Disease, Firuzgar Hospital, Tehran, Iran

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Date of Web Publication30-Dec-2010


This study was performed to study the immune response to hepatitis B virus (HBV) vaccine in health-care workers. Through a cross-sectional study, relevant information and blood samples from 151 healthcare workers at the Firuzgar hospital were studied. The age range of the study individuals was 20-59 years, with the mean and standard deviation being 35.11 and 10.06, respectively. There were 24 males (15.9%) and 127 females (84.1%). The mean and median of months after HBV vaccination was 63.42 and 49.00, respectively. The mean and median of anti­HBs titer in those who received HBV vaccination was 164.81 and 200 milli international units per milliliter (mIU/mL), respectively. Of the 129 HBV-vaccinated subjects, 103 (68.2%) had anti­HBs titer >10 and 26 (17.2%) had anti-HBs titer <10. There was no association between gender and anti-HBs titer, but vaccination and adequate completion of its courses were associated with higher anti-HBs titer (P < 0.05). Also, the logistic regression method showed that the association between duration after vaccination and age with anti-HBs titer was not statistically significant. Our study suggests that the HBV vaccine immunization program had obtained excellent efficacy. There is need for further investigation among subjects who are not vaccinated against HBV but are positive for anti-HBs as well as in HBV-vaccinated subjects with low anti-HBs titers, about possible low-level viremia and other causes of lower vaccine efficacy, particularly in health-care workers.

How to cite this article:
Zamani F, Fallahian F, Hashemi F, Shamsaei Z, Alavian SM. Immune response to hepatitis B vaccine in health-care workers. Saudi J Kidney Dis Transpl 2011;22:179-84

How to cite this URL:
Zamani F, Fallahian F, Hashemi F, Shamsaei Z, Alavian SM. Immune response to hepatitis B vaccine in health-care workers. Saudi J Kidney Dis Transpl [serial online] 2011 [cited 2022 Aug 18];22:179-84. Available from: https://www.sjkdt.org/text.asp?2011/22/1/179/74350

   Introduction Top

In a study, a model was developed to calculate the age-specific risk of acquiring hepatitis B virus (HBV) infection, acute hepatitis B (ill­ness and death) and progression to chronic HBV infection. The effect of hepatitis B vacci­nation was calculated from vaccine efficacy and vaccination series coverage, with and with­out the administration of the first dose of vac­cine within 24 hours of birth (i.e., birth dose) to prevent perinatal HBV infection. For the year 2000, the model estimated that 620,000 per­sons died worldwide from HBV-related causes: 580,000 (94%) from chronic infection-related cirrhosis and hapatocellular carcinoma and 40,000 (6%) from acute hepatitis B. In the surviving birth cohort for the year 2000, the model estimated that, without vaccination, 64.8 million would become HBV infected and 1.4 million would die from HBV-related disease. Routine infant HBV vaccination, with 90% co­verage and the first dose administered at birth, would prevent 84% of the global HBV-related deaths. [1]

A mass campaign of immunization against hepatitis B was undertaken for those born from 1989 to March 2007 in Iran. During this cam­paign, 1,320,000 people were vaccinated and about 90% coverage was reached. Hepatitis B vaccination takes years if not decades to show effectiveness in the community. In 2002, con­sidering the country's health needs and prio­rities, the program also recommended vacci­nating people with high-risk occupations like firefighters, workers of city hall, etc. It was con­cluded that 12% of the first target group was already vaccinated against HBV. The health infrastructure to expand the coverage for more vaccination is accessible in Iran, and this ap­proach will decrease the incidence rate in the Iranian population, especially if followed by these considerations: educating the people, es­pecially the at-risk group; implementing stra­tegies to prevent transmission to others and screening and finding the patients in early stages and asymptomatic phase. [2]

Although protective anti-HBs response rates after HBV vaccination typically exceed 90%, a number of factors can impede an adequate an­tibody response. Smoking, obesity, injection into the buttock, chronic liver disease, presence of human leukocyte antigens (HLA)-DR3, DR7 and DQ2 alleles, absence of the HLA-A2 allele and extremes of age may be associated with reduced immunogenicity. The response rates are also lower in immunocompromised patients, such as transplant recipients, patients receiving chemotherapy and those with end-stage liver disease. Patients with chronic kidney disease should be vaccinated early in the course of their disease, before the renal disease progresses, to ensure optimal response to vaccination. [3]

In Iran, Cuban hepatitis B vaccine became available approximately in 1994 and mass vac­cination of neonates and children was incor­porated in the national vaccination scheme. [4] Healthcare workers (HCWs) are at a high risk of acquiring HBV. The seroconversion rate after HBV vaccination in Pakistani HCWs was similar to that reported in the western and neighboring populations. HCWs with a reduced immune response to HBV vaccine in a high­disease-prevalent population are at greater risk. Therefore, it is crucial to check post-vacci­nation HBsAb in all the HCWs. This strategy will ensure safety at work by reducing noso­comial transmission and will have a cost­effective impact at an individual as well as a national level, which is very much desired in a resource-limited country. [5]

In this manuscript, the immune response to HBV vaccine in HCWs at the Firuzgar Hos­pital, who had been immunized by HBV vac­cine, is studied.

   Methods Top

The immune response to HBV vaccine in 151 hospital employees of the Firuzgar Hospital was investigated. They were questioned as to whether they had received HBV vaccine be­fore or not and, if vaccinated, were asked whe­ther they had completed three courses of the vaccine. All individuals who had not received HBV vaccine earlier or those vaccinated with anti-HBs titer equal to or less than 10 mIU/mL were assessed. One hundred and forty (92.7%) of them were medical personnel, including nur­ses and laboratory technicians, and 11 (7.3%) were hospital-cleaning staff. Distribution of anti-HBs antibodies and its correlations was studied. Participants signed the consent form and the proposal was approved by the local ethics committee of the hospital.

   Statistical Analysis Top

Statistical analyses were performed using SPSS statistical software (version 16.0, 2007; SPSS). Frequencies were obtained by direct counting. Data of samples were analyzed by a chi square goodness of fit test and logistic regression method. The correlations were compared by chi square test and logistic regression method, res­pectively. The odds ratio (OR) and 95% con­fidence interval (CI) for the occurrence were computed. All two-tailed P-values of <0.05 were considered to be statistically significant.

   Results Top

The age range of the study individuals was 20-59 years, and the mean and standard de­viation were 35.11 and 10.06, respectively. There were 24 males (15.9%) and 127 females (84.1%). At the time of sampling, 129 subjects (85.4%) had received HBV vaccine earlier and 22 (14.6%) had not. Among the vaccinated subjects, according to the subjects' statement, 113 had completed the three courses of HBV vaccination and 16 cases had not. Of the 151 subjects studied, 35 (23.2%) had anti-HBs titer <10 and 116 (76.8%) had anti-HBs titer more than 10 mIU/mL. Of the 129 HBV-vaccinated subjects, 103 (68.2%) had HBsAb titer >10 and 26 (17.2%) had HBsAb titer <10 mLU/mL. The difference between anti-HBs titer in those vaccinated (129, 85.4%) and those not vacci­nated (22, 14.6%) was significant (X 2 : 4.546, P-value: 0.033). The difference between anti­HBs titer in the medical personnel and the cleaning staff was not significant (X 2 : 1.158, P-value: 0.282).

Our results show that variables of gender and medical health workers versus cleaning staff in the hospital were not associated with anti-HBs titers (P > 0.05). However, variables of vaccina­tion and completeness of its course were posi­tively associated with anti-HBs titer (P < 0.05) [Table 1]. Also, the logistic regression method shows that association between length of time after vaccination and age with anti-HBs titer was not statistically significant [Table 2].
Table 1: Distribution and correlation of anti-HBs titer with the variables.

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Table 2: Correlations and prediction of anti-HBs titer with age and date of vaccination by logistic regression.

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The mean and median of months after HBV vaccination were 63.42 and 49.00, respec­tively. The mean and median of anti-HBs titer in those who received HBV vaccination were 164.81 and 200, respectively. Among the HBV­vaccinated subjects (129), the difference in anti­HBs titer between those who completed versus those who did not complete the course of vac­cination, by independent samples T-test, was not significant [Table 3].
Table 3: Statistical difference between anti-HBs titer in those who completed versus those who did not complete the course of vaccination.

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   Discussion Top

The results of our study suggest that it is ne­cessary to investigate the possible low-level viremia and other causes of lower immune res­ponse to HBV vaccine in HCWs. Hepatitis B vaccines are highly effective and safe and have been incorporated into national immunization programs in over 150 countries. The major hu­moral immune response is to the common determinant of the surface antigen protein of the virus. [6] In a study of 538 children who had received three doses of Cuban hepatitis B vaccine, 305 (56.7%) were good responders, 149 (27.7%) were hyporesponders and 84 (15.6%) were non-responders. In this study, the con­centration of anti-HBs in good responders was low and the rate of hyporesponders and non­responders was high. This suggests that anti­HBs titer should be measured in all Iranian vaccinees after the third dose of vaccination with the Cuban HBV vaccine, such that the health authorities can decide which scheme of vaccination is to be implemented. [4]

Lack of adequate HBsAb formation may be due to the persistent exposure of HCWs to HBV infection and low-level viremia or, also, infection with mutant forms from patients on certain anti-viral treatments. In a study, 94 ne­gative HBsAg, negative anti-HBs and positive anti-HBc cases and 56 persons with negative HBsAg, anti-HBs and anti-HBc controls were vaccinated with recombinant hepatitis B vac­cine. A higher percent of married cases toge­ther with a higher percent of positive HBsAg in spouses may explain the slight difference in the response to vaccination in the case group in comparison with the control group as a result of a booster-like effect, which seldom happens because of recurrent contacts between the subjects and the HBsAg-positive spouses. [7]

An interventional, descriptive study conduc­ted on children who had been immunized with Cuban recombinant hepatitis B vaccine repor­ted that their antibody titers were <10 mIU/mL (non-responder), while these was 10-100 mIU/ mL (hyporesponder) in those who received a booster dose of the same vaccine in their del­toid muscles. The response of these 141 chil­dren, whose mean age was 1.9 years, to the booster dose of vaccine was 94.3% and 100% with the first and second booster dose of the vaccination, respectively. The study demons­trated moderately increased antibody produc­tion in the majority of vaccines with single sup­plementary vaccine. [8]

Among 600 HCWs interviewed in a referral hospital in Shiraz, Iran, 339 subjects were vac­cinated with three doses of HBV vaccine. The anti-HBsAb titers were >100 mIU/mL in 211 subjects (62.2%), 10-100 mIU/mL in 85 (25.1%) and <10 mIU/mL in 43 (12.7%) persons. Among these subjects, 273 were vaccinated when they were <5 years old, 47 cases were vaccinated when they were between 5 and 10 years of age and 19 cases were vaccinated when they were aged more than 10 years. The majority of the study subjects had an antibody concentration above the protective level. Re-assessment for vaccination should be considered in HCWs according to their anti-HBsAb levels 10 years after vaccination. [9]

Vaccination of healthy adults with recombi­nant hepatitis B (rHB) vaccine fails to induce a protective antibody response in a proportion of individuals. Imbalanced T-helper 1 (Th1)/Th2 response has been attributed to the lack of specific antibody response to rHB vaccine. In a study, in vitro production of interleukin-2 (IL-2), interferon (IFN)-gamma and IL-10 was investigated in Iranian healthy adults vaccina­ted with the rHB vaccine. Peripheral blood mononuclear cells (PBMC) were isolated from 18 high-responders and eight non-responders and stimulated with rHB antigen or phytohema­glutinin (PHA) mitogen. The results demons­trated a significant decrease in the production of IL-2, IFN-gamma and IL-10 (P < 0.005) in response to the rHB antigen. The levels of all cytokines induced by PHA were similarly re­presented in both groups of vaccinees. These findings suggest that unresponsiveness to rHB vaccine may be caused by inadequate Th1- and Th2-like cytokine production. [10]

The persistence of anti-HBs depends on the peak antibody level achieved after three do­ ses. [11],[12],[13],[14] Unresponsiveness to HB vaccine has been attributed to a number of environmental and genetic factors, the most important ones being the haplotype of HLA antigens and im­munological tolerance. [15] A variety of HLA class I and II antigens have been reported to be associated with unresponsiveness to the vaccine in different ethnic populations. [16]

Different responses of clonal selection to the immunizing antigen in different human popu­lations mean that any definition of anamnestic response must recognize the role of ethnicity.

There remain problems with interpreting the long-term protection against HBV infection. Follow-up studies are needed for surveillance of break-through infections. Also, sub-clinical in­fections (formation of anti-HBc in the absence of HBsAg) need to be distinguished from ac­tual breakthrough infections (presence of HBs Ag and clinical disease). Furthermore, in coun­tries where the endemicity of hepatitis B is low, clinically significant breakthrough infec­tions (as a marker of waning immunity) will be rare. For studies in developing or highly ende­mic countries, further complications for inter­pretation include maternal hepatitis B status, dose and route of immunization of infant, the frequent lack of documentation of post-immu­nization response, other infections (in parti­cular, HIV infection) and nutritional status. [17]

In conclusion, the HBV vaccine immuniza­tion program had obtained excellent efficacy and immune response in HCWs. Causes of vac­cine failure and HBV variants need to be asses­sed in this group. This study showed the need for further immunologic and molecular invest­tigation in subjects with no HBV vaccination but positive anti-HBs and also in HBV-vacci­nated subjects with a low level of anti-HBs titer about the possible low-level viremia and causes of lower efficacy, respectively, in HCWs.

   Acknowledgment Top

The authors would like to thank Mr. Jafar Anisi, Mrs. Azam Eskandari and Mr. Sabze­vari for the accompanying illustrations and for their support and technical assistance.

   References Top

1.Goldstein ST, Zhou F, Hadler SC, Bell BP, Mast EE Margolis HS. A mathematical model, to estimate global hepatitis B disease burden and vaccination impact. Int J Epidemiol 2005; 34(6):1329-39.  Back to cited text no. 1
2.Alavian. SM. Ministry of health in Iran is serious about controlling hepatitis B. Editorial­Hepatitis Monthly 2007;7(1):3-5.  Back to cited text no. 2
3.Perrillo R, Nair S. Hepatitis B and D. Chapter 75, pages: 1666-9: Feldman M, Friedman L S, Brandt LJ.(Eds): Sleisenger and Fordtran's Gastrointestinal and liver disease Pathophysiology/ Diagnosis/ Management 8th Edition 2006 Saunders Elsevier Inc.  Back to cited text no. 3
4.Dahifar H. Immunogenicity of Cuban hepatitis B vaccine in Iranian children. Arch Iranian Med 2004;7(2):89-92.  Back to cited text no. 4
5.Zeeshan M, Jabeen K, Ali AN, et al. Evaluation of immune response to Hepatitis B vaccine in health care workers at a tertiary care hospital in Pakistan: an observational prospective study. BMC Infect Dis 2007;7:120.  Back to cited text no. 5
6.Zuckerman JN. Protective efficacy, immunotherapeutic potential, and safety of hepatitis B vaccines. J Med Virol 2006;78(2):169-77.  Back to cited text no. 6
7.Kabir A, Keshvari M, Kashani AH, Alavian SM. Predicting response to HBV vaccination in people with positive anti-HBc but negative HBsAg and anti-HBs. Hum Vaccin 2008;4(5):379-83.  Back to cited text no. 7
8.Dahifar H, Mousavi F, Ghorbani A. Response of Booster Dose of Cuban Recombinant Hepatitis-B Vaccine in Nonresponder and Hyporesponder Children. Pak J Med Sci 2007;23(1):23-6.  Back to cited text no. 8
9.Saberifiroozi M, Gholamzadeh S, Serati AR. The long-term immunity among health care workers vaccinated against hepatitis B virus in a large referral hospital in southern Iran. Arch Iran Med 2006;9(3):204-7.  Back to cited text no. 9
10.Kardar GA, Jeddi-Tehrani M, Shokri F. Diminished Th1 and Th2 cytokine production in healthy adult nonresponders to recombinant hepatitis B vaccine. Scand J Immunol 2002;55(3):311-4.  Back to cited text no. 10
11.Hadler SC, Francis DP, Maynard JE, et al. Long-term immunogenicity and efficacy of hepatitis B vaccine in homosexual men. N Engl J Med 1986;315:209-14.  Back to cited text no. 11
12.Tilzey A, Palmers SI, Banatvala JE, Vines SK, Gilks WR. Hepatitis B vaccine boosting among young healthy adults. Lancet 1994;344:1438-9.  Back to cited text no. 12
13.Amani A, Shokri F. Immunogenicity of recom­binant hepatitis B vaccine in Iranian neonates. Iranian J Med Sci 1995;20:87-92.  Back to cited text no. 13
14.Hadler SC, Margolis HS. Hepatitis B immunization: vaccine types, efficacy, and indications for immunization. Curr Clin Top Infect Dis 1992;12:282-308.  Back to cited text no. 14
15.Chisari FV, Ferrari C. Hepatitis B virus immuno­pathogenesis. Ann Rev Immunol 1995;13:29-60.  Back to cited text no. 15
16.Martinetti M, Cuccia M, Daielli C, et al. Anti­HBV neonatal immunization with recombinant vaccine. Part II. Molecular basis of the impaired alloreactivity. Vaccine 1995;13:555-60.  Back to cited text no. 16
17.Fitzsimons D, Francois G, Hall A, et al. Long­term efficacy of hepatitis B vaccine, booster policy, and impact of hepatitis B virus mutants. Vaccine 2005;23(32):4158-66.  Back to cited text no. 17

Correspondence Address:
Farhad Zamani
Gastroenterintestinal and Liver Disease Research Center, Iran University of Medical Sciences, Firuzgar Hospital, Vali asr Square, Aban St., Tehran
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Source of Support: None, Conflict of Interest: None

PMID: 21196642

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  [Table 1], [Table 2], [Table 3]

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